This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Abstract of project: Recent large-scale genetic epidemiology studies have identified newly defined susceptibility genes for Type 2 Diabetes. However, the pathobiological mechanisms by which these putative disease susceptibility loci predispose to diabetes remains to be further defined. The goal of the study is to determine whether genetic markers such as DNA variants in the zinc transporter SLC30A8 or the transcription factor 7-like 2 (TCF7L2) genes can be used to identify individuals with increased susceptibility to impaired beta-cell function and the eventual development of diabetes within an at risk African American population (AA). The specific aims are: 1) Establish a well-phenotyped sample of overweight/obese, non-diabetic African-American subjects that undergo careful characterization of glucose/insulin metabolism in the GCRC setting and 2) Determine if variants in SLC308A8 and TCF7L2 genes are associated with impaired insulin secretion in overweight/obese African Americans. These studies should eventually lay the groundwork for 'Predictive Health'models based on genetic markers that will enable clinicians to more effectively identify high-risk pre-diabetic patients and target preventive interventions.